Efficacy of polyurethane graft on cyclodextrin to control drug release for tumor treatment.

Hydrophilicity of cyclodextrin is controlled through grafting of polyurethane of varying graft density, thereby maintain the hydrophilic-hydrophobic balance, to sustain the drug delivery rate for better tumor treatment. Grafting is verified through nuclear magnetic resonance (1H NMR) and other spectroscopic techniques along with the hydrodynamic volume measurement of grafted species and the degree of substitution has been calculated from the integrated peak areas. Thermal and mechanical stability of the graft copolymers have improved significantly with respect to cyclodextrin and the formation of smaller blobs having larger in number has been obtained from small angle neutron scattering, atomic force microscopy and optical images. Sustained drug delivery has been achieved using graft copolymer as opposed to burst release in pure cyclodextrin and polyurethane and the phenomenon is understood from the specific interactions, as observed though spectroscopic and thermal measurement, between graft copolymer and drug followed by this novel architecture of the graft copolymers. Biocompatibility of graft copolymers has been checked using cellular studies through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell adhesion. Importantly, the cell killing efficiency has been demonstrated by embedding anti-cancer drug in polymer matrices causing mortality rate of 80% using graft copolymer against meagre 20% using pure drug or drug embedded in cyclodextrin and the result is realised from the sustained release of drug from the graft copolymer vis-à-vis burst release in other systems. Cellular studies have been translated into an animal model showing the efficacy of newly developed patch, made of drug embedded in copolymer, towards the significant suppression of tumors in mice as compared to control. Histopathological images and biochemical parameters indicate the normal body organ/blood in copolymer treated mice against severely damaged organ especially liver/blood in the mice treated with pure drug or drug embedded in cyclodextrin arising from burst release. Thus, graft copolymer with unique architecture is found to be an effective drug delivery vehicle for melanoma cancer treatment without side effect.

In Vitro Evaluation of Carbachol and Endothelin on Contractility of Colonic Smooth Muscle in Hirschsprung's Disease.

Background: The hypomotility of colon observed in Hirschsprung's disease (HD) has been attributed to congenital aganglionosis only. So far, it is not clear whether the contractility of colonic smooth muscle in this condition is altered or not. Therefore, the present study attempted to understand the contractile status of colonic segments of HD patients by examining carbachol and endothelin (ET-1) evoked colonic smooth muscle contractions in vitro . Methods: Contractile responses were recorded from strips of colonic segments obtained from HD patients, using organ bath preparations. Cholinergic agonist carbachol and ET-1 along with their antagonists were used to evoke contractile responses. Thereafter, the samples were histopathologically confirmed for HD. Results: Colonic strips of HD did not show any spontaneous contractions but responded to carbachol and ET-1 to a lesser extent. In HD, response of carbachol was blocked by atropine and hexamethonium by nearly 73% and 50% respectively. ET-1 induced contractile responses were blocked by ET-A and ET-B antagonist up to 40%, signifying the possible role of ET-A and ET-B receptors in HD colon contractility. Conclusion: As evidenced by lack of spontaneous contractions and impaired carbachol and ET-1-induced contractile responses, it is concluded that, in addition to aganglionosis, decreased contractility of colonic smooth muscle may contribute to hypomotility observed in patients with HD.